Epidemiology

Seizures are a common complaint of patients seeking care in emergency departments (EDs). By some estimates, seizures account for 1% to 2% of all ED visits.^1,2 Epilepsy, a condition resulting in recurrent, unprovoked seizures, affects upward of 4 million people; however, as much as 10% of the population will have at least one seizure during their lifetime.^3,4

The natural history of untreated epilepsy is essentially unknown. Based on retrospective data, it was found that 32% of patients with a first epileptic seizure will experience a second attack within 1 month, 51% within 3 months, and 87% within the first year. Some strong predictors for recurrence of seizures include a history of previous neurologic insult, abnormal findings on neurologic examination, or an electroencephalogram (EEG) with epileptiform abnormalities and circadian timing. Approximately 50% patients in whom epilepsy is diagnosed will become seizure free with only single-drug treatment. The addition of a second or third drug will control another 20%, and intractable seizures that are poorly responsive to standard medical treatment will develop in about 30%.

Pathophysiology

Seizures are the result of inappropriate electrical activity in the brain, whereas syncope is caused primarily by transient hypoperfusion within the brain. Uncontrollable electrical discharges can originate from a single area as a result of an underlying structural condition (e.g., tumor, scar, bleeding), or it can be caused by an imbalance in inhibitory (γ-aminobutyric acid [GABA]) and excitatory (N-methyl-D-aspartate) receptor activities. The latter is usually due to toxic or metabolic causes.

The specific seizure activity is determined by the area in the brain involved (Box 99.1). Some of these abnormal electrical discharges may remain localized, whereas others may involve larger areas of the brain. Subsequently, the resultant clinical spectrum includes isolated focal motor activity, as well as generalized motor and sensory abnormalities, including altered mental status and behavioral changes.

Presenting Signs and Symptoms

If available, the previous medical history may reveal risk factors (Box 99.2) associated with the development of seizures. The history can be obtained from the patient (after normalization of mental status), family, primary care physicians, old medical records, or emergency medical service (EMS) personnel.

Differential Diagnosis and Medical Decision Making

The most common serious condition that can be misinterpreted as a seizure is syncope.⁵ There may be important clinical signs or preceding events that can help differentiate these two entities (Table 99.1). In many circumstances patients will be unable to provide critical information, so it is important to try to obtain an accurate description from anyone who witnessed the event (e.g., family, coworkers, EMS personnel). Aside from syncope, several other medical conditions need to be included in the differential diagnosis of seizures (Boxes 99.3 and 99-4; Table 99.2).

Table 99.1 Seizure Disorder versus Syncope

Table 99.2 Seizure Work-up

AIDS, Acquired immunodeficiency syndrome; CNS, central nervous system; HIV, human immunodeficiency virus.

Though rare, various disturbances in electrolytes may precipitate seizures, including hyponatremia, uremia, and hypocalcemia. A serum electrolyte assay is recommended for patients with new-onset seizures. Between 2.4% and 8% of patients with seizures will have electrolyte abnormalities. Despite the fact that the majority of these abnormalities will be clinically insignificant, they should be evaluated and can often be easily corrected in the ED.

If an overdose is suspected, both blood and urine toxicologic screens should be performed.

Measuring the serum prolactin level has no clinical utility in the ED because the results cannot be obtained in a timely manner. However, it may be useful for the consulting service that will conduct further work-up to help differentiate between epileptic (generalized tonic-clonic or complex partial seizures) and psychogenic nonepileptic seizures. It should be performed within 10 to 20 minutes after a suspected event. Prolactin levels of at least twice baseline are considered abnormal (positive). Prudent clinicians may decide to have prolactin levels measured, especially in patients with the symptoms suggestive of nonepileptic or psychogenic seizures.⁶

An electrocardiogram (ECG) should be obtained in every patient with a first onset of seizures or with suspicion of a cardiac cause of decreased central nervous system (CNS) perfusion. In addition to ischemia, the most important disorders that have to be excluded are related to conduction abnormalities and consequent dysrhythmias. ECGs are used to evaluate widening of the QRS complex because of sodium channel blockade after an overdose of certain medications, particularly cyclic antidepressants. More specific changes on the ECG, such as a terminal 400-msec R wave in the aVR lead, can also assist in identifying toxicity from cyclic antidepressants. A prolonged QTc interval can be found with overdose of citalopram (a selective serotonin reuptake inhibitor with proconvulsive properties). Tachyarrhythmias are often seen in the setting of cocaine and methylxanthine toxicity (theophylline, caffeine) (Box 99.5).

Patients at high risk for meningitis or encephalitis should be treated with ceftriaxone (2 g intravenously [IV]), vancomycin (1 g IV), and acyclovir (500 mg IV), even before the results of a spinal tap are available. In addition, patients should be placed in an isolation room with droplet precautions.

Neurocysticercosis (NCC) is the most common parasitic CNS infection in the world and has been increasing in the United States since 1980.⁷ In endemic areas (Latin America, Asia, Africa), NCC is considered to be main cause of late-onset epilepsy, and seizures are reported to be the most common symptom and occur in 70% to 90% of patients. The majority of patients will respond to treatment with phenytoin or carbamazepine.

Albendazole is the mainstay antiparasitic drug for the treatment of NCC (15 mg/kg/day divided into two doses twice daily for 8 to 30 days). Patients in whom NCC is diagnosed may require treatment with steroids to control the inflammation and treat meningitis, cysticercal encephalitis, and angiitis. Treatment is usually started with dexamethasone (4 to 12 mg/day), and it can be replaced with prednisone (1 mg/kg/day) for long-term treatment.

Computed tomography (CT) of the brain should be performed in every patient with a first onset of seizures and in those with persistent change in mental status, focal neurologic deficit, or suspicion of an organic intracerebral lesion. Early CT scanning is essential for identifying surgically correctable causes. If there is a concern that trauma occurred, CT can be used to rule out cervical spine and intracerebral injury (Box 99.6).

Magnetic resonance imaging (MRI) is more sensitive than CT and can be effective in diagnosing additional lesions; namely, temporal sclerosis, cortical dysplasia, vascular malformations (e.g., arteriovenous aneurysms), and some tumors. Its use will depend on availability and time constraints, but MRI is not typically done on an emergency basis. The majority of patients will be able to undergo MRI as an outpatient.

The EEG records brain electrical activity and is used for definitive diagnosis of epilepsy and related conditions. The need for EEG in the emergency setting is limited, usually to patients whose seizure activity is uncontrollable despite aggressive treatment or to patients whose seizure activity is more difficult to diagnose.

Intubated patients who are paralyzed or have undergone induction of phenobarbital coma and general anesthesia should be monitored continuously with an EEG to exclude seizure activity because in these situations obvious seizure activity may not be apparent as a result of neuromuscular paralysis. Another indication may be patients who have unexplained altered consciousness that can be due to persistent non–tonic-clonic seizure activity.

If patient is transported by EMS, multiple steps in the treatment (Fig. 99.1) protocol can be initiated and completed by EMS personnel, including administration of anticonvulsants, airway protection, correction of glucose, and elicitation of the initial history, including drug exposure. it is essential that an attempt be made to control seizure activity immediately on arrival at the ED, so discussion of treatment will occur simultaneously with discussion of the diagnostic approach. Maintenance of adequate cerebral perfusion and consequent oxygen and glucose supply to the brain is the goal of treatment.

Fig. 99.1 Steps in treatment.

abx, Antibiotics; AIDS, acquired immunodeficiency syndrome; CBC, complete blood count; C-spine, cervical spine; CT, computed tomography; ECG, electrocardiogram; EEG, electroencephalogram; β-HCG, β-human chorionic gonadotropin; HIV, human immunodeficiency virus; Hx, history; IV, intravenous; LP, lumbar puncture; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; r/o, rule out.

Most seizures will stop spontaneously or soon after the initiation of appropriate treatment. One of the primary goals during the evaluation and treatment of patients with seizures is to preserve a patent airway and oxygenation, as well as prevent aspiration in patients who are in the postictal phase. Despite very dramatic signs and symptoms, including cyanosis, very few patients who are actively experiencing seizures will require endotracheal intubation.

Cessation of motor seizure activity as a result of chemical paralysis does not indicate cessation of neuronal seizure activity. It is essential that clinicians continue to closely monitor for seizures in intubated patients, including, eventually, EEG monitoring. While awaiting placement of the EEG electrodes, clinicians should use the pupillary reflex as an indicator of seizure activity. In a paralyzed patient, the pupillary light reflex remains intact. Lack of a pupillary light reflex should suggest ongoing seizure activity.

A rapid bedside or field fingerstick test should be performed immediately to evaluate for low serum glucose. One ampule of 50% dextrose is administered IV to a hypoglycemic patient. It should be repeated if the patient remains hypoglycemic. Glucagon, 1 mg intramuscularly (IM) or subcutaneously, should be given to hypoglycemic patients without intravenous access as a temporizing measure. Glucagon, however, can cause vomiting, thus increasing the risk for aspiration in an unresponsive or seizing patient.

Benzodiazepines should be administered immediately because they have been shown to control the majority of seizures regardless of cause through an increase in GABA activity. Studies have shown that lorazepam (Ativan, 0.05 to 0.1 mg/kg up to a maximum of a 4-mg initial dose) is more effective than diazepam (Valium, 5 to 15 mg IV) for the initial control of seizures, although both agents are acceptable.^2,4 If intravenous access is difficult, intramuscular or rectal administration of valium (Diastat, rectal form of valium, 0.2 mg/kg up to 20 mg PR) or lorazepam (0.1 to 0.2 mg/kg IM) is an alternative. Intranasal midazolam (Versed) has also been used. Continued seizure activity should be treated with a second dose of a benzodiazepine, along with the addition of a second agent (e.g., barbiturate, propofol, pyridoxine/vitamin B₆) and attention to disorders inciting the seizure (e.g., increased intracranial pressure, CNS infection, eclampsia, drug-related seizures) (Table 99.3).

Phenytoin (Dilantin) is a second drug of choice but requires patient monitoring when administered IV. A loading dose of 15 to 20 mg/kg should be started simultaneously with the administration of benzodiazepines. This should be done for patients with elevated intracranial pressure (e.g., tumor, bleeding, hydrocephalus), as well as for those who are not compliant with the phenytoin prescribed. Phenytoin has poor water solubility and has to be formulated with propylene glycol, so intravenous delivery is rate-limited (no faster than 50 mg/min) to prevent hypotension.

If the emergency physician suspects drug-induced seizures, including withdrawal (alcohol, sedative-hypnotics, baclofen), phenytoin should not be used as a second drug of choice because it has disadvantageous properties (negative inotropic and proarrhythmogenic properties). For drug-related seizures resistant to benzodiazepines, barbiturates, propofol, and pyridoxine should be considered.

Fosphenytoin (Cerebyx) is less irritating to veins, less toxic to tissues, and less likely to induce dysrhythmias and can be administered either IV or IM, but it is more expensive. Fosphenytoin is a prodrug of phenytoin. Plasma phosphatase enzymes cleave phenytoin from fosphenytoin, which takes 8 to 15 minutes when administered IV. With intramuscular dosing, approximately 30 minutes is needed for therapeutic levels to be achieved. The loading dose is 15 to 20 mg/kg (phenytoin equivalent) IV or IM. Fosphenytoin is water soluble and associated with far less tissue toxicity at the infusion site; however, it is just as cardiotoxic as phenytoin. Fosphenytoin is typically reserved for short-term parental administration.

Barbiturates are potent respiratory depressants, much more so than benzodiazepines, so clinicians should be concerned about the potential for intubation. Traditionally, phenobarbital (10 to 20 mg/kg IV administered at a rate of 25 to 50 mg/min) has been used as a drug of choice, but because of rate-limited administration, pentobarbital (100 mg IV administered at a rate of 25 mg/min), a shorter-acting barbiturate, should be considered for resistant seizures.

Patients whose seizure activity has ceased before arrival at the ED might be candidates for oral loading of antiepileptic medications. The oral loading regimen for patients who have no detectable serum level of phenytoin (Dilantin) is 20 mg/kg in divided doses administered over a day, with a maximum dose of 400 mg every 2 hours. A suspension formulation is preferred over tablets because of better absorption and higher serum levels. Adverse reactions to phenytoin, such as ataxia, somnolence, and confusion, are decreased with a slower loading rate.

The usual typical outpatient oral dose is 100 mg three times per day. Because the half-life of phenytoin is about 24 hours, some patients take 300 mg once a day. The therapeutic serum level is 10 to 20 mg/L. Even at this level, some patients will experience mild sedation and cognitive effects. With long-term use, gum and skin thickening can occur and may not be reversible. One in 10,000 will experience Steven-Johnson syndrome. Phenytoin can cause folate deficiency, which leads to anemia and bone problems, so daily use of multivitamins is recommended.

Patients with chronic seizures who have a typical event may require only evaluation of the antiepileptic level and triggering factors. However, new organic pathology that may lower the seizure threshold (e.g., infection, electrolyte abnormality, trauma) should be excluded. Any precipitating factors that may unmask a chronic seizure disorder or explain an increase in seizure reoccurrence in patients with therapeutic levels of anticonvulsants should be identified (see Box 99.4). In the absence of concomitant pathology, the majority of patients with chronic seizures can be discharged home if they return to baseline.

In addition to the classic or traditional anticonvulsants (phenytoin, carbamazepine, phenobarbital), the emergency physician may encounter many new anticonvulsants. The majority of new drugs do not have timely measurable serum levels.

Patients who are undergoing chronic anticonvulsant treatment should receive an additional oral dose before discharge if the level is found to be subtherapeutic. It is also reasonable to give a dose of one of the newer anticonvulsants in the ED to patients who are noncompliant with treatment (Table 99.4).

Neurology consultation should be considered for patients in status epilepticus (SE) or for breakthrough seizures. Trauma and neurosurgery consultation should be obtained for patients with intracranial bleeding and complex trauma. Finally, an infectious disease consultation could be considered for some patients with infectious pathology and acquired immunodeficiency syndrome (AIDS).

Special Circumstances

Follow-up, Next Steps in Care, and Patient Education

Every patient with persistent seizures, change in mental status, or underlying medical condition that requires hospital treatment (e.g., sepsis, overdose, trauma) should be admitted. Patients in SE should be admitted to an intensive care setting (Box 99.8).

Patients with a chronic seizure disorder can be discharged if they return to their normal baseline neurologic level (Box 99.9). If the drug level is found to be subtherapeutic, an additional dose of antiepileptics should be given prior to discharge. Before discharge, patients may inquire about their prognosis. In the absence of precipitating factors, secondary seizures may be avoidable in the future, but there will always be some risk, depending on the underlying condition and lifestyle. Patients should avoid sleeplessness, heavy alcohol use, and other physiologic stressors that can alter seizure thresholds.